PinX1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis by suppressing MMP-2 via NF-κB-dependent transcription.
PinX1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis by suppressing MMP-2 via NF-κB-dependent transcription.
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DOI：
10.18632/oncotarget.4011
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发表时间：
2015-08-28
期刊：
影响因子：
--
通讯作者：
Zheng JN
中科院分区：
文献类型：
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作者：
Li HL;Han L;Chen HR;Meng F;Liu QH;Pan ZQ;Bai J;Zheng JN
PIN 2/TRF 1相互作用的端粒酶抑制因子1（PinX 1）是一个新克隆的基因，被认为是维持端粒酶活性、端粒酶长度和染色体稳定性的主要单倍不足肿瘤抑制因子。本研究旨在探讨PinX 1在肾透明细胞癌（ccRCC）中的临床意义和生物学功能。在两个独立的人ccRCC群组中使用组织微阵列和免疫组织化学染色来评估PinXl在ccRCC中的临床相关性。我们的数据表明，与正常肾组织和配对的相邻非肿瘤组织相比，在ccRCC组织中PinX 1表达显著降低。PinX 1低表达与患者的浸润深度、淋巴结转移和晚期TNM分期显著相关，并且与总体和疾病特异性生存率较差相关。考克斯回归分析显示PinX 1表达是ccRCC患者的独立预后因素。此外，PinX 1通过NF-κ B依赖性转录抑制MMP-2的表达和活性，抑制ccRCC的迁移和侵袭。体内研究证实PinX 1负性调节ccRCC的转移和MMP-2和NF-κB-p65的表达。这些发现表明PinX 1抑制ccRCC转移，并可能作为ccRCC候选临床预后标志物和潜在的治疗靶点。
PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene which has been identified as a major haploinsufficient tumor suppressor essential for maintaining telomerase activity, the length of telomerase and chromosome stability. This study explored the clinical significance and biological function of PinX1 in human clear cell renal cell carcinoma (ccRCC). The clinical relevance of PinX1 in ccRCC was evaluated using tissue microarray and immunohistochemical staining in two independent human ccRCC cohorts. Our data demonstrated that PinX1 expression was dramatically decreased in ccRCC tissues compared with normal renal tissues and paired adjacent non-tumor tissues. Low PinX1 expression was significantly correlated with depth of invasion, lymph node metastasis and advanced TNM stage in patients, as well as with worse overall and disease-specific survival. Cox regression analysis revealed that PinX1 expression was an independent prognostic factor for ccRCC patients. Moreover, PinX1 inhibited the migration and invasion of ccRCC by suppressing MMP-2 expression and activity via NF-κB-dependent transcription in vitro. In vivo studies confirmed that PinX1 negatively regulated ccRCC metastasis and the expression of MMP-2 and NF-κB-p65. These findings indicate that PinX1 suppresses ccRCC metastasis and may serve as a ccRCC candidate clinical prognostic marker and a potential therapeutic target.